Milk-alkali syndrome

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Milk-alkali syndrome
Classification and external resources
ICD-9 275.42
DiseasesDB 8215
MedlinePlus 000332
eMedicine article/123324

In medicine, milk-alkali syndrome, also called Burnett's syndrome in honor of Charles Hoyt Burnett (1913–1967), the American physician who first described it,[1][2] is characterized by hypercalcemia caused by repeated ingestion of calcium and absorbable alkali (such as calcium carbonate, or milk and sodium bicarbonate). If untreated, milk-alkali syndrome may lead to metastatic calcification and renal failure.

It was most common in the early 20th century, but there has been a recent[when?] increase in the number of cases reported.[3][4]

Pathophysiology[edit]

The name "milk-alkali syndrome" derives from when patients would take in excessive amounts of milk and antacids to control their dyspepsia, leading to over-ingestion of two key ingredients that lead to the disorder, excess calcium and excess base. Ingesting over two grams of elemental calcium per day produces this disorder in susceptible individuals. Gastrointestinal absorption of such a large amount of calcium leads to hypercalcemia. This inhibits parathyroid hormone secretion by the parathyroid gland and may also lead to diabetes insipidus. The body's attempt to rid itself of the excess base in the urine may cause bicarbonaturia and subsequent hypovolemia due to transport of sodium ions to accompany the bicarbonate.[citation needed]

Hypovolemia may increase the reabsorption of calcium and bicarbonate in the proximal convoluted tubules of the kidney. Elevated bicarbonate levels in the blood raises the pH, producing an alkalemia. In this state, excess bicarbonate eventually begins to reach the distal convoluted tubule, leading to sodium retention in the lumen, an effect similar to the action of thiazide diuretics, hence increasing lumen positivity and driving calcium through the passive calcium channels to bind intracellular calbindin. Finally, because of the decreased intracellular sodium, there is an increased driving force for the basolateral Na+/Ca++ antiporter, thus facilitating calcium reabsorption. Basically, hypovolemia is the culprit that prevents correction of the hypercalcemia.[citation needed]

A simpler mechanism: Increased calcium intake causes a hypercalcemia in individuals who maintain an elevated fractional absorption of calcium even with increased calcium intake. The hypercalcemia does two things: 1. It prevents PTH release and 2. It causes a Nephrogenic Diabetes Insipidus (where the tubules are less responsive to ADH). The decreased PTH results in an increased reclamation of bicarbonate by the proximal tubule, causing an alkalosis. [It is known that the increased PTH of primary hyperparathyroidism is a cause of Type II (proximal) Renal Tubular Acidosis which is characterized by a decreased bicarbonate reclamation in the PCT.] The NDI leads to water loss and hypovolemia which result in activation of Renin-Angiotensin-Aldosterone System and lead of a contraction alkalosis due to the high aldosterone levels. Both things result in Alkalosis and the hypovolemia further exacerbates the hypercalcemia keeping the cycle going.[citation needed]

The understanding of this mechanism led to the development of a simple and elegant treatment for hypercalcemia.[citation needed] The first and most important step is intravenous infusion of normal saline to restore the intravascular volume, which reverses the calcium and bicarbonate retention in the PCT.[citation needed] Then a loop diuretic is used, but only after the volume replacement is complete, otherwise volume contraction would result, which would further exacerbate the hypercalcemia.[citation needed] The loop diuretics inhibit the Na-K-2Cl symporter and hence eliminate passive diffusion of potassium into the lumen via the ROMK channel. This effectively removes the net positive charge from the lumen, one of the main driving forces for calcium reabsorption via the paracellular pathway. In addition, loop diuretics increase the flow of luminal contents, which helps flush the calcium to the distal nephron.[citation needed]

Clinical[edit]

Effects due to hypercalcemia caused by Primary Hyperparathyroidism may be remembered by the mnemonic bones, stones, groans and psychiatric overtones [ or moans ] while sitting on a throne.[citation needed] Milk alkali syndrome is a cause of secondary hyperparathyroidism. This means an increased risk of kidney stones due to the hypercalcemia, but not bone fractures as bone is not being resorped, anorexia, vomiting, constipation, weakness, abdominal pain and a host of psychiatric effects, including depression, fatigue and altered mental status.[citation needed] Thus, a level of serum calcium must be obtained, but a full workup must include total/ionized calcium, albumin, phosphate, PTH, PTHrP, vitamin D and TSH. In addition, evaluation of hypercalcemia must include an ECG, which may show a short QT interval.[citation needed]

References[edit]

  1. ^ synd/4029 at Who Named It?
  2. ^ Burnett CH, Commons RR, Albright F, Howard JE (1949). "Hypercalcemia without hypercalcuria or hypophosphatemia, calcinosis and renal insufficiency; a syndrome following prolonged intake of milk and alkali". N. Engl. J. Med. 240 (20): 787–94. doi:10.1056/NEJM194905192402001. PMID 18126919. 
  3. ^ Caruso JB, Patel RM, Julka K, Parish DC (July 2007). "Health-behavior induced disease: return of the milk-alkali syndrome". J Gen Intern Med 22 (7): 1053–5. doi:10.1007/s11606-007-0226-0. PMC 2219730. PMID 17483976. 
  4. ^ Beall DP, Henslee HB, Webb HR, Scofield RH (May 2006). "Milk-alkali syndrome: a historical review and description of the modern version of the syndrome". Am. J. Med. Sci. 331 (5): 233–42. doi:10.1097/00000441-200605000-00001. PMID 16702792. 

External links[edit]

  • eMedicine.com - Milk-Alkali Syndrome ([1]).